Aurothioglucose/Benzydamine Hydrochloride 27 2. Albazzaz MK, et al. Alveolitis and haemolytic anaemia induced Profile that have occurred with benoxaprofen include skin disorders, by azapropazone. BMJ 1986; 293: 1537–8. Bendazac is an NSAID (p.96) structurally related to indometacin notably photosensitivity reactions but also erythema multiforme 3. Montgomery RD, Babb RG. Alveolitis and haemolytic anaemia (p.66). It has been used topically in preparations containing 1 or and the Stevens-Johnson syndrome, onycholysis and other nail induced by azapropazone. BMJ 1987; 294: 375. 3% for the treatment of various inflammatory skin disorders. disorders, gastrointestinal disturbances including peptic ulcera- Effects on the gastrointestinal tract. In a review1 of the rel- Bendazac lysine has been used in the management of cataract, tion and bleeding, blood disorders such as thrombocytopenia, ative safety of 7 oral NSAIDs, the UK CSM commented that eye drops containing 0.5% being instilled three times daily. cholestatic jaundice and other liver or biliary disorders, and renal azapropazone was associated with the highest risk of gastrointes- Hepatotoxicity has been reported. failure. tinal reactions in both epidemiological studies and an analysis of spontaneous reporting of adverse reactions. Although it appeared ◊ References. that some patients over 60 years of age had received doses ex- 1. Balfour JA, Clissold SP. Bendazac lysine: a review of its phar- ceeding those recommended for this age group, it was considered macological properties and therapeutic potential in the manage- Benzydamine Hydrochloride (BANM, USAN, rINNM) that even when this was taken into account a marked difference ment of cataracts. Drugs 1990; 39: 575–96. 2. Prieto de Paula JM, et al. Hepatotoxicidad por bendazaco: análi- AF-864; Benzidamin Hidroklorür; Benzindamine Hydrochloride; remained between gastrointestinal reactions for azapropazone sis de 16 casos. Rev Clin Esp 1995; 195: 387–9. Benzydamine, Chlorhydrate de; Benzydamini Hydrochloridum; compared with other NSAIDs. Preparations Benzydaminy chlorowodorek; Hidrocloruro de bencidamina. 3- The CSM recommended that azapropazone should be restricted (1-Benzyl-1H-indazol-3-yloxy)-NN-dimethylpropylamine hydro- to use in rheumatoid arthritis, ankylosing spondylitis, and acute Proprietary Preparations (details are given in Part 3) Austria: Versus; Gr.: Versalba; Ital.: Bendalina; Versus; Philipp.: Bendalina; chloride. gout and only when other NSAIDs have been ineffective. Its use Port.: Bendalina; Venez.: Bendalina. in patients with a history of peptic ulceration was contra-indicat- Бензидамина Гидрохлорид ed. It was also recommended that when used in patients over 60 C19H23N3O,HCl = 345.9. years of age for rheumatoid arthritis or ankylosing spondylitis CAS — 642-72-8 (benzydamine); 132-69-4 (benzydam- the dose should be restricted to a maximum of 600 mg daily. Benorilate (BAN, rINN) ine hydrochloride). Azapropazone has been withdrawn in many countries including Benorilaatti; Benorilat; Bénorilate; Benorilato; Benorilatum; ATC — A01AD02; G02CC03; M01AX07; M02AA05. the UK. Benorylate; FAW-76; Fenasprate; Win-11450. 4-Acetamidophe- ATC Vet — QA01AD02; QG02CC03; QM01AX07; QM02AA05. 1. CSM/MCA. Relative safety of oral non-aspirin NSAIDs. Cur- nyl O-acetylsalicylate. rent Problems 1994; 20: 9–11. Also available at: http:// www.mhra.gov.uk/home/idcplg?IdcService=GET_ Бенорилат FILE&dDocName=CON2015615&RevisionSelectionMethod= C17H15NO5 = 313.3. LatestReleased (accessed 01/11/07) CAS — 5003-48-5. ATC — N02BA10. Effects on the skin. Of 917 reports of adverse reactions asso- N ciated with azapropazone forwarded to the WHO Collaborating ATC Vet — QN02BA10. Centre for International Drug Monitoring1 before September N 1984, 190 (21%) were of photosensitivity. Of 154 reports of pho- CH O 3 tosensitivity evaluated a causal relationship to use of azapropa- H O N zone was considered certain in 6, probable in 138, and possible N CH3 in 10. In May 1994 the UK CSM stated2 that since 1976 they had 3C OH O CH3 received 464 reports of photosensitivity reactions associated with azapropazone and commented that, when corrected for pre- O (benzydamine) scription volume, reporting of this reaction was 50 times greater O than with other commonly prescribed NSAIDs. They recom- Pharmacopoeias. In Br. and Pol. mended that patients should be advised to avoid direct exposure BP 2008 (Benzydamine Hydrochloride). A white crystalline to sunlight or to use sunblock preparations. powder. Very soluble in water; freely soluble in alcohol and in 1. Olsson S, et al. Photosensitivity during treatment with azapropa- Pharmacopoeias. In Br. and Chin. BP 2008 (Benorilate). A white or almost white, odourless or al- chloroform; practically insoluble in ether. A 10% solution in wa- zone. BMJ 1985; 291: 939. ter has a pH of 4.0 to 5.5. 2. CSM/MCA. Photosensitivity associated with azapropazone most odourless, crystalline powder. Practically insoluble in wa- (Rheumox). Current Problems 1994; 20: 6. Also available at: ter; sparingly soluble in alcohol and in methyl alcohol; soluble in Adverse Effects http://www.mhra.gov.uk/home/idcplg?IdcService=GET_ acetone and in chloroform. After topical application to the skin local reactions such as ery- FILE&dDocName=CON2015616&RevisionSelectionMethod= LatestReleased (accessed 01/11/07) Profile thema or rash may occur and photosensitivity has been reported. After use as mouth and throat preparations, numbness or stinging Porphyria. Azapropazone is considered to be unsafe in patients Benorilate is an aspirin-paracetamol ester with analgesic, anti- inflammatory, and antipyretic properties. After absorption, it is sensations of the oral mucosa have been reported; hypersensitiv- with porphyria because it has been shown to be porphyrinogenic ity reactions including urticaria, photosensitivity, and bronchos- in animals. rapidly metabolised to salicylate and paracetamol. It has been used orally in the treatment of mild to moderate pain (see Choice pasm may also occur rarely. Preparations of Analgesic, p.2) and fever (p.10). It has also been used in oste- Effects on the kidneys. A 57-year-old woman who had used BP 2008: Azapropazone Capsules; Azapropazone Tablets. oarthritis, rheumatoid arthritis, and soft-tissue rheumatism. 400 g of a topical cream containing benzydamine hydrochloride Proprietary Preparations (details are given in Part 3) When an overdose of benorilate is suspected, it has been suggest- 3% over a period of 4 months was found to have raised plasma Arg.: Debelex†; Austria: Prolixan†; Gr.: Prolixan†; Hung.: Prolixan†; Irl.: ed that plasma concentrations of both salicylate and paracetamol concentrations of creatinine and urea consistent with a substan- Rheumox†; Port.: Prolixan†; S.Afr.: Rheumox; Turk.: Prodisan; UK: Rheu- should be measured since a normal plasma-paracetamol concen- tial reduction in glomerular filtration rate.1 mox†. tration cannot necessarily be assumed from a normal plasma-sal- 1. O’Callaghan CA, et al. Renal disease and use of topical non- icylate measurement. steroidal anti-inflammatory drugs. BMJ 1994; 308: 110–11. ◊ References. Effects on the skin. Photoallergic contact dermatitis devel- Bendazac (BAN, USAN, rINN) 1. Aylward M. Toxicity of benorylate. BMJ 1973; 2: 118. oped on the hands of a 65-year-old woman after the use of a gen- 1 AF-983; Bendazaco; Bendazacum; Bindazac. (1-Benzyl-1H-inda- 2. Symon DNK, et al. Fatal paracetamol poisoning from benorylate ital wash containing benzydamine 0.1% for several years. The zol-3-yloxy)acetic acid. therapy in child with cystic fibrosis. Lancet 1982; ii: 1153–4. lesions disappeared once the patient stopped using the solution. Preparations 1. Lasa Elgezua O, et al. Photoallergic hand eczema due to benzy- Бендазак damine. Eur J Dermatol 2004; 14: 69–70. BP 2008: Benorilate Oral Suspension; Benorilate Tablets. C16H14N2O3 = 282.3. 1 CAS — 20187-55-7. Proprietary Preparations (details are given in Part 3) Overdose. A 6-year old girl had hallucinations after receiving 500 mg of benzydamine orally; it had been intended as a vaginal ATC — M02AA11; S01BC07. Belg.: Duvium†; Fr.: Salipran†; Irl.: Benoral†; Switz.: Duvium†; UK: Beno- ral†. douche for pruritus vulvae; recovery was spontaneous. ATC Vet — QM02AA11; QS01BC07. 1. Gómez-López L, et al. Acute overdose due to benzydamine. Hum Exp Toxicol 1999; 18: 471–3. OH Benoxaprofen (BAN, USAN, rINN) Uses and Administration O Benoksaprofeeni; Bénoxaprofène; Benoxaprofeno; Benoxapro- Benzydamine hydrochloride is an NSAID (p.99). It is used topi- fenum; Compound 90459; LRCL-3794. 2-[2-(4-Chlorophe- cally on the skin in concentrations of 3 to 5% in painful muscu- loskeletal and soft-tissue disorders. Benzydamine hydrochloride O nyl)benzoxazol-5-yl]propionic acid. is also used as a mouthwash or spray in concentrations of 0.15% Беноксапрофен for the relief of inflammatory conditions of the mouth and throat. C H ClNO = 301.7. N 16 12 3 It has been given orally or rectally for the relief of painful and CAS — 51234-28-7. inflammatory conditions, and as a topical solution for vaginal ir- N ATC — M01AE06. rigation. ATC Vet — QM01AE06. Benzydamine salicylate (benzasal) has been used topically on the skin as a 6% cream or spray. O Mouth disorders. Results of a randomised placebo-controlled study in patients undergoing radiotherapy for oropharyngeal can- Cl COOH cer indicated that benzydamine as an oral rinse was effective in Bendazac Lysine (BANM, rINNM) N reducing the area and severity of mucositis.1 Benzydamine is AF-1934; Bendazac lisina; Bendazacum Lysinum. L-Lysine-(1-ben- also used locally for the management of mouth ulcers (p.1700) 2 zyl-1H-indazol-3-yloxy)acetic acid. CH3 although an early study found it no more useful than placebo. Бендазак Лизин 1. Epstein JB, et al. Benzydamine HCl for prophylaxis of radiation- Profile induced oral mucositis: results from a multicenter, randomized, C22H28N4O5 = 428.5. Benoxaprofen is an NSAID (p.96) structurally related to ibupro- double-blind, placebo-controlled clinical trial. Cancer 2001; 92: CAS — 81919-14-4. fen (p.64). It was formerly given orally in rheumatoid arthritis 875–85. ATC — S01BC07. and osteoarthritis but because of reports of adverse reactions and 2. Matthews RW, et al. Clinical evaluation of benzydamine, chlo- ATC Vet — QS01BC07. rhexidine, and placebo mouthwashes in the management of re- fatalities the manufacturers halted worldwide marketing of the current aphthous stomatitis. Oral Surg Oral Med Oral Pathol Pharmacopoeias. In Chin. preparation known as Opren in the early 1980s. Adverse effects 1987; 63: 189–91. The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii) 28 Analgesics Anti-inflammatory Drugs and Antipyretics

Preparations Bicifadine Hydrochloride (USAN, rINNM) fects have been reported with other ophthalmic NSAID prepara- BP 2008: Benzydamine Cream; Benzydamine Mouthwash; Benzydamine Bicifadina, hidrocloruro de; Bicifadine, Hydrochloride de; Bicifadi- tions; for further details see under Adverse Effects of Diclofenac, p.45. Oromucosal Spray. ni Hydrochloridum; CL-220075. (±)-1-p-Tolyl-3-azabicyclo- Proprietary Preparations (details are given in Part 3) [3.1.0]hexane hydrochloride. 1. Asai T, et al. Three cases of corneal melting after instillation of Arg.: Actifedrin; Bencifem; Ernex; Sandival Desleible; Austral.: Difflam; Dif- a new nonsteroidal anti-inflammatory drug. Cornea 2006; 25: flam Anti-inflammatory Throat Spray; Difflam Solution; Austria: Tantum; Бицифадина Гидрохлорид 224–7. Tantumar; Braz.: Benflogin; Benzitrat; Ciflogex; Eridamin†; Flogin-Ped†; Fl- ogo Rosa; Flogolab; Flogoral; Fonergoral; Neoflogin; Canad.: Sun-Benz†; C12H15N,HCl = 209.7. Preparations Tantum; Cz.: Rosalgin; Tantum; Denm.: Andolex; Fr.: Opalgyne; Ger.: Ta n - CAS — 71195-57-8 (bicifadine); 66504-75-4 (bicifadine tum Rosa; Tantum Verde; Gr.: Tant um ; Hong Kong: Dantum; Difflam; Ve- hydrochloride). Proprietary Preparations (details are given in Part 3) rax; Hung.: Tantum Verde; Indon.: Tanflex; Tantum; Irl.: Difflam; Israel: Jpn: Bronuck; USA: Xibrom. Easy gel; Ital.: Afloben; Benzirin; Ginesal; Lagin†; Multum†; Saniflor Colluto- rio; Tantum; Verax; Xentafid; Malaysia: Difflam Anti-inflammatory Lozeng- es; Difflam Solution; Mex.: Artroben; Lonol; Vantal; Neth.: Tantum; NZ: HN Difflam; Philipp.: Difflam; Pol.: Hascosept; Tantum; Port.: Flogoral; Momen; Rosalgin; Tantum; Tantum Rosa; Tantum Verde; Rus.: Tantum Rose Bufexamac (BAN, rINN) (Тантум Роза); Tantum Verde (Тантум Верде); S.Afr.: Andolex; Singa- Bufeksamaakki; Bufeksamakas; Bufexamaco; Bufexamacum; pore: Difflam; Spain: Agilona; Fulgium; Rosalgin; Tantum; Tantum Verde; Swed.: Andolex; Switz.: Bucco-Tantum; Thai.: Difflam; Turk.: Benzidan; Bufexamák; Bufexamak. 2-(4-Butoxyphenyl)acetohydroxamic ac- Tanflex; Tantum; Ternex; UK: Difflam; Venez.: Azutan; Bevi Dam; Biozendi; id. Flodont; Ginacol; Tantum; Tantum Verde; Zydan. Буфексамак Multi-ingredient: Arg.: Buchex; Dresan Biotic†; Dresan†; Ernex Duo; Espectocural; Pentadent†; Austral.: Difflam Anti-inflammatory Lozenges C12H17NO3 = 223.3. with Cough Suppressant; Difflam Lozenges; Difflam Mouth Gel; Difflam-C; CAS — 2438-72-4. Logicin Rapid Relief; Braz.: Angino-Rub; Hong Kong: Difflam Anti-inflam- CH3 matory Lozenges; Difflam Mouth Gel; Difflam-C; Logicin Rapid Relief; ATC — M01AB17; M02AA09. Hung.: Tantum Rosa; Ital.: Algolisina†; Gola Action; Linea F; Mediplus; (bicifadine) ATC Vet — QM01AB17; QM02AA09. Malaysia: Difflam Anti-inflammatory Lozenges (with Antibacterial); Dif- flam Anti-Inflammatory Lozenges (with cough suppressant); Difflam Mouth Gel; Difflam-C; Mex.: Lonol Sport; NZ: Difflam Cough; Difflam Mouth Gel; Profile Difflam-C; Port.: Benoral; Gartun; Tantum Verde; S.Afr.: Andolex-C; Sin- Bicifadine hydrochloride is a novel analgesic under investigation H gapore: Difflam Anti-inflammatory Anti-Bacterial Lozenges; Difflam Mouth for the treatment of painful conditions including postoperative N Gel; Difflam-C; Spain: Bristaciclina Dental; Dolosarto†; Etermol Antitusivo; OH Mentamida; Prosturol; Tantum; Vinciseptil Otico; Turk.: Kloroben; Venez.: dental pain. Amicets; Gencivol Compuesto; Solunovar Compuesto. O H3C O Bornyl Salicylate Benzyl Nicotinate Pharmacopoeias. In Eur. (see p.vii) and Jpn. Borneol Salicylate; Salicilato de bornilo. 2-Hydroxybenzoic acid . A white or almost white, crystalline Bensylnikotinat; Bentsyylinikotinaatti; Benzil Nikotinat; Benzyli Ph. Eur. 6.2 (Bufexamac) 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl ester. powder. Practically insoluble in water; soluble in dimethylfor- Nicotinas; Nicotinato de bencilo. Benzyl pyridine-3-carboxylate. Борнилсалицилат mamide; slightly soluble in ethyl acetate and in methyl alcohol. C13H11NO2 = 213.2. Protect from light. CAS — 94-44-0. C17H22O3 = 274.4. CAS — 560-88-3. Profile Bufexamac is an NSAID (p.96) that is applied topically in con- N centrations of 5% in various skin disorders. Stinging and burning CH3 may occur after application; hypersensitivity reactions have been H3C O HO reported.

H3C O Preparations O Proprietary Preparations (details are given in Part 3) Arg.: Parfenac†; Austral.: Paraderm†; Austria: Bufex; Bufexan; Droxaryl; Pharmacopoeias. In Ger. O Parfenac; Belg.: Bufexine†; Droxaryl†; Cz.: Droxaryl†; Fr.: Parfenac; Ger.: Bufederm†; duradermal; Haemo-Exhirud Bufexamac; Jomax; Malipuran; Profile Parfenac; Windol; Ital.: Fansamac; Viafen; Neth.: Droxaryl; Parfenac; Port.: Benzyl nicotinate is used in topical preparations as a rubefacient. Profile Parfenac; Switz.: Parfenac. Bornyl salicylate is a salicylic acid derivative that has been used Preparations Multi-ingredient: Austral.: Paraderm Plus; Resolve; Austria: Droxaryl; topically in rubefacient preparations similarly to methyl sali- Cz.: Mastu S; Ger.: Faktu akut; Hamo-ratiopharm N; Hamoagil plus; Mastu Proprietary Preparations (details are given in Part 3) cylate (p.85) for the relief of pain in musculoskeletal and joint S; Hong Kong: Fungo Soothing Balm; Mastu S; Hung.: Mastu S; NZ: Para- Ger.: Leukona-Aktiv-Rheumabad†; Pernionin Thermo Teilbad; Pernionin disorders. derm Plus; Rus.: Proctosan (Проктозан); Thai.: Mastu S. Thermo Vollbad; Pykaryl T; Rubriment; Rubriment-BN. Multi-ingredient: Arg.: Butidiona†; Oxa Sport; Pergalen; Austria: Am- Preparations benat; Derivon; Expectal-Balsam; Igitur-antirheumatische; Igitur-Rheumaflu- Proprietary Preparations (details are given in Part 3) id; Menthoneurin; Mobilisin plus; Rheumex; Rubizon-Rheumagel; Rubri- (rINNM) ment; Thermo-Rheumon; Thrombophob; Braz.: Etrat†; Trombofob; Multi-ingredient: Ger.: Forapin E†; Switz.: Forapin†; Hygiodermil. Bumadizone Calcium Chile: Bayro-Therm†; Cz.: Dolo-Rubriment†; Rheuma-Salbe†; Rubriment- Bumadizona cálcica; Bumadizone Calcique; Calcii Bumadizonum. N†; Thermo-Rheumon†; Fin.: Trombosol; Fr.: Lumbalgine; Ger.: ABC Warme-Salbe†; Ambene N; Arthrodestal N†; Auroanalin Thermo; Cam- Calcium 2-(1,2-diphenylhydrazinocarbonyl)hexanoate hemihy- phopin; Capsamol N†; Caye Rheuma-Balsam; Cor-Select†; DoloVisano Bromfenac Sodium (USAN, rINNM) drate. Salbe†; Emasex-N†; Forapin E†; Hot Thermo; Lomazell forte N†; Lumbinon Thermo†; mikanil†; Ostochont†; Pelvichthol N; Phardol Rheu- AHR-10282; AHR-10282B; Bromfénac Sodique; Bromfenaco Кальций Бумадизон ma†; Phardol Warme-Balsam†; Phlogont-Thermal; Praecordin S†; Rheu- sódico; Natrii Bromfenacum. Sodium [2-amino-3-(p-bromoben- (C19H21N2O3)2Ca, ⁄ H2O = 699.8. balmin Thermo†; Rheuma-Salbe N; Rheuma-Salbe†; Rheumasalbe†; Rheu- zoyl)phenyl]acetate sesquihydrate. masan N†; Rheumasit†; Rubriment; Rubriment-N†; Tachynerg Campher CAS — 3583-64-0 (bumadizone); 34461-73-9 (bumadi- Herzsalbe; Thermo-Menthoneurin†; Thermo-Rheumon N†; Thermo- Натрий Бромфенак zone calcium). Rheumon†; Thermosenex; Togal Mobil-Gel†; Warme-Gel†; zuk thermo†; C15H11BrNNaO3,1 ⁄ H2O = 383.2. ATC — M01AB07. Gr.: Bayolin; Ehrlich; Striafissan†; Thermo-Roiplon; Hong Kong: Salome- CAS — 91714-94-2 (bromfenac); 91714-93-1 (brom- thyl; Hung.: Bayolin†; Thermo-Rheumon†; India: Beparine; K5 Hair Tinc- ATC Vet — QM01AB07. ture†; Thrombophob; Indon.: Stop X; Thrombophob; Zeropain; Ital.: Sa- fenac sodium); 120638-55-3 (bromfenac sodium). lonpas; Sloan; Mex.: Bayro Termo; Pol.: Lumbolin; Thermo-Rheumon; Port.: Adrinex†; Balsamo Analgesico; Medalginan; Rus.: Capsicam (Капсикам); Heparin Ointment (Гепариновая Мазь); Switz.: Assan ther- Br mo; Demotherm Pommade contre le rhumatisme†; Dolo Demotherm; Forapin†; Histalgane; Marament-N; Thermocutan†; Turk.: Thermo-Doline; HO Thermo-Rheumon; Thermoflex; UK: Salonair; Venez.: Ehrlich Balsamo. NH2 O NH Beta-aminopropionitrile N O Aminopropionitrile; β-Aminopropionitrile; β-Aminopropionitri- O lo; BAPN. 3-Aminopropionitrile. O OH Бета-аминопропионитрил (bromfenac) C3H6N2 = 70.09. CH3 CAS — 151-18-8 (beta-aminopropionitrile); 1119-28-4 Profile (beta-aminopropionitrile fumarate). Bromfenac sodium, a phenylacetic acid derivative related to di- (bumadizone) ATC Vet — QM01AX91. clofenac (p.44), is an NSAID (p.96). It is instilled twice daily as 0.1% eye drops for ocular pain and inflammation including post- Profile operative inflammation in patients who have undergone cataract NH Bumadizone calcium is an NSAID (p.96) that is metabolised to 2 extraction. When used postoperatively, it may be started 24 hours phenylbutazone (p.117) and oxyphenbutazone (p.107). Use has N after surgery and continued for the next 14 days. been limited by the risk of agranulocytosis and other haemato- It was formerly given orally in the management of acute pain but logical adverse effects. Profile was withdrawn from the market after reports of severe and some- Beta-aminopropionitrile, a lysyl oxidase inhibitor, is an anti-in- times fatal hepatic failure. Preparations flammatory used as the fumarate in veterinary medicine for the (details are given in Part 3) Effects on the eyes. Severe corneal melting (ulceration) was Proprietary Preparations treatment of tendinitis. seen in 3 patients after topical use of bromfenac sodium.1 All Mex.: Desflam. patients recovered after bromfenac was withdrawn. Similar ef-